BOSTON, November 21, 2017 – The Institute for Clinical and Economic Review (ICER) today released an Evidence Report assessing the comparative clinical effectiveness and value of three vesicular monoamine transporter-2 (VMAT2) inhibitors for management of tardive dyskinesia (TD), a movement disorder often associated with long-term use of certain antipsychotic drugs. The report reviews evidence on valbenazine (Ingrezza®, Neurocrine Biosciences) and deutetrabenazine (Austedo®, Teva), both approved earlier this year for treatment of TD, as well as tetrabenazine (Xenazine®, Lundbeck), which is approved for use in Huntington’s disease but has also been used to treat TD.
This Evidence Report will be the subject of an upcoming public meeting of the New England Comparative Effectiveness Public Advisory Council (New England CEPAC) in Newton, MA on December 5, 2017. The New England CEPAC is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.
“Valbenazine and deutetrabenazine represent potentially important advances for people living with a condition that can have significant effects on their quality of life and daily function,” noted Dan Ollendorf, PhD, ICER’s Chief Scientific Officer. “While the evidence is promising, uncertainty remains around the true spectrum of clinical benefit and long-term safety with these treatments, and current prices are far out of alignment with the benefits measured in clinical trials. Our hope is that our report and public meeting can spur conversation among stakeholders to work towards strategies to support continued research and innovation in this area while ensuring that pricing and coverage decisions do not create undue barriers to patient access.”
A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report reflects changes made based on comments received from patient groups, clinicians, the manufacturers of the drugs, and other stakeholders. Detailed responses to public comments can be found here.
Key Report Findings
For treatment of TD in adults who have previously used certain antipsychotic drugs, evidence is promising but inconclusive for both valbenazine and deutetrabenazine. This designation was based largely on uncertainty surrounding key outcome measures studied in trials, along with an absence of long-term comparative safety data. Evidence was insufficient to assess the net health benefit of tetrabenazine.
Economic analyses found that the cost-effectiveness of both valbenazine and deutetrabenazine far exceed commonly cited thresholds of $50,000-$150,000 per quality-adjusted life year (QALY), at $752,000 and $1.1 million per QALY, respectively. Tetrabenazine was not included in analyses due to data limitations. While cost-effectiveness findings were improved by accounting for potential — though currently unproven — improvements in adherence to treatments for underlying psychiatric disorders, they remained unfavorable.
To align with the benefit provided to patients, valbenazine’s annual wholesale acquisition cost (WAC) would need to fall between $7,600 and $11,260, a discount of 85% – 90% from its current price of $76,000. Deutetrabenazine’s annual WAC of $90,000 would need to be lowered by 90% – 93%, to $6,200 – $9,200.
ICER’s review also considered additional benefits of the medications not included in clinical trials. People living with TD, as well as caregivers and other stakeholders, suggested that better control of TD symptoms may decrease caregiver burden, make it easier to find or maintain a job, and improve control of the underlying psychiatric disorder. These and other concerns may also influence decisions around treatment of TD.
The Evidence Report, accompanying voting questions, all public comments received on the draft report, and ICER’s written response to comments, are available on the ICER website.
During the December public meeting, pre-registered stakeholders will provide brief oral comments on the report and its findings, the New England CEPAC will vote on key questions raised in the report, and a roundtable of experts will discuss recommendations for applying the evidence to policy and practice. Requests to make an oral comment were accepted during the public comment period on the Draft Evidence Report and are now closed.
Registration for the in-person meeting is open here. Registration for a live webcast of the meeting is open here.